ascorbic-acid and Heart-Diseases

Cardiac surgery is associated with oxidative stress and systemic inflammation, which both contribute to postoperative organ dysfunction. Vitamin C is a pleiotropic, antioxidant, and potentially organ-protective micronutrient. Past clinical trials and meta-analyses have focused predominantly on occurrence of postoperative atrial fibrillation. Therefore, we investigated the influence of perioperative vitamin C administration on clinically relevant parameters closer related to the patient's recovery, especially organ function, and overall outcomes after cardiac surgery.. Randomized controlled trials (RCTs) comparing perioperative vitamin C administration versus placebo or standard of care in adult patients undergoing cardiac surgery were identified through systematic searches in Pubmed, EMBASE, and CENTRAL on 23 November 2018. Published and unpublished data were included. Assessed outcomes include organ function after cardiac surgery, adverse events, in-hospital mortality, intensive care unit, and hospital length-of-stay. Data was pooled only when appropriate.. A total of 19 RCTs with 2008 patients were included in this meta-analysis. Vitamin C significantly decreased the incidence of atrial fibrillation (. Vitamin C impacts clinically and economically important outcomes, such as ICU and hospital length-of-stay, duration of mechanical ventilation and lowers the incidence of atrial fibrillation. Due to missing reports on organ dysfunction, this meta-analysis cannot answer the question, if vitamin C can improve single- or multiorgan function after cardiac surgery.

Topics: Ascorbic Acid; Cardiac Surgical Procedures; Heart Diseases; Humans; Perioperative Care; Vitamins

A potential interaction involving therapeutic doses of ascorbic acid and warfarin is described.. A 65-year-old Caucasian man with chronic cardiac and pulmonary disorders was admitted to the emergency room for chest pain, shortness of breath, nausea, and diaphoresis. Imaging scans showed acute pulmonary embolism and deep venous thrombosis of the lower extremities. Anticoagulation therapy (enoxaparin 60 mg twice daily) was initiated on the day of admission; warfarin sodium (5 mg daily) was initiated on the next day. After admission to the hospital, the patient continued to use several home medications and vitamins, including ascorbic acid, which he reported taking for three months to facilitate the absorption of oral supplemental iron. For more than a week, his International Normalized Ratio (INR) values remained below target as the dosage of warfarin was gradually increased to 20 mg daily. After potential contributors to warfarin resistance (e.g., impaired liver or renal function, clotting factor abnormalities) were ruled out, ascorbic acid use was discontinued on hospital day 8. The patient's INR rapidly increased to a high of 15.4 on hospital day 10, requiring intervention with phytonadione therapy and the suspension of warfarin use. On day 12, with an INR of 2.7, the patient was restarted on warfarin therapy; he was discharged three days later with stable INR values.. A patient who was unable to achieve anticoagulation during concurrent treatment with warfarin and ascorbic acid experienced a rapid increase in INR to above-target values after the discontinuation of ascorbic acid use, suggesting that the vitamin might have had an inhibitory effect on warfarin.

Topics: Aged; Ascorbic Acid; Drug Interactions; Drug Resistance; Heart Diseases; Humans; International Normalized Ratio; Male; Warfarin

Experimental evidence indicates a strong connection between oxidative damage, cancer, and aging. Epidemiological observations suggest that a diet rich in fruits and vegetables is associated with lower incidence of some cancers and longer life expectancy; since fruits and vegetables contain natural antioxidants, a considerable effort has been dedicated to understanding their effects in experimental studies and in human trials.. A: Effects of antioxidant-containing food and supplements on oxidation damage in humans. Intervention trials employing a variety of biomarkers have shown either a slight decrease in oxidation damage or no effect. B: Effects of selected antioxidants on mortality and cancer incidence. β-carotene and α-tocopherol, alone or in combination, increase cardiovascular and all-cause mortality or have no effect. In some studies, β-carotene and retinyl palmitate significantly increase the progression of lung cancer and aggressive prostate cancer. Protection against cardiovascular mortality or no effect of vitamin E has been reported, with an increase of all-cause mortality at dosages greater than 150 IU/day. Selenium showed beneficial effects on gastrointestinal cancer and reduced the risk of lung cancer in populations with lower selenium status. For multivitamin and mineral supplementation, no significant reduction of mortality or cancer incidence was observed, but some reports indicate a possible preventive effect in cervical cancer.. The majority of supplementation studies indicate no variation of general mortality and of cancer incidence or a detrimental effect on both. Antioxidant supplements so far tested seem to offer no improvement over a well-balanced diet, possibly because of the choice of the substances tested or of an excessive dosage. However, new natural or synthetic compounds effective in vitro and in experimental studies might still be worth investigating in human trials.

Topics: Aging; alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Dietary Supplements; Diterpenes; Heart Diseases; Humans; Incidence; Life Expectancy; Neoplasms; Randomized Controlled Trials as Topic; Retinyl Esters; Selenium; Trace Elements; Vitamin A; Vitamin E; Vitamins

The prevalence of coronary artery disease and heart failure is increasing in modern industrialized countries, fueling the search for novel therapies. Because metabolism and function in the heart are inextricably linked, energy substrate metabolism has provided a potential target for novel therapies and the development of technologies to image myocardial metabolism has been crucial in establishing new therapeutic approaches. Nuclear imaging probes have been used to successfully evaluate aerobic fatty acid metabolism, anaerobic glucose metabolism, and oxidative metabolism and can be used for the accurate, sensitive, and physiological evaluation of therapeutic effects. More recently, with the advent of stem-cell technologies, imaging approaches have been employed to track the fate of stem cells and to monitor the success of these treatments. In the future, our ability to image myocardial metabolism is likely to assist the development of other new therapies to improve the function of the failing heart.

Topics: Ascorbic Acid; Fatty Acids; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Glucose; Heart Diseases; Humans; Iodine Radioisotopes; Iodobenzenes; Myocardium; Positron-Emission Tomography; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

Heart disease is the number one cause of death in the United States and has long been recognized to be multifactorial. A growing body of evidence suggests that not only free radical-mediated reactions but also inflammatory responses play major roles in atherogenesis. Vitamin E has both antioxidant and antiinflammatory properties and is the most widely studied vitamin in clinical trials and thus will be the primary example used in this review. Clinical trials of vitamin E efficacy, in hindsight, have been overly optimistic in their expectation that a vitamin could reverse poor dietary habits and a sedentary lifestyle as well as provide benefit beyond that of pharmaceutical agents in treating heart disease. However, it is also apparent that most Americans do not consume dietary amounts adequate to meet established vitamin E requirements. In response to oxidative stressors, vitamin E can decrease biomarkers of lipid peroxidation, is itself killed, and requires optimal vitamin C status to function most effectively. Thus, adequate vitamin E intakes are clearly needed, but what is adequate for what function has yet to be defined. It is noteworthy that in most trials, biomarkers were not used nor were oxidative stress and lipid peroxidation markers used or plasma vitamin E concentrations measured.

Topics: Antioxidants; Ascorbic Acid; Biomarkers; Cholesterol; Dietary Supplements; Evidence-Based Medicine; Heart Diseases; Humans; Life Style; Lipid Peroxidation; Nutritional Requirements; Oxidative Stress; Vitamin E

Antioxidants in foods and supplements are being widely promoted for their health benefits. Protection from heart disease is one claim that seems compelling in light of scientific evidence and large-scale observational studies. But will antioxidant supplements help your patients? To examine this question, Dr Tran reviews numerous clinical studies and evaluates the discrepancies between observational and clinical results.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Dietary Supplements; Heart Diseases; Humans; Vitamin E

The deleterious effects of cigarette smoking on antioxidant protection and chronic disease risk are well known. Recent studies show that exposure of nonsmokers to environmental tobacco smoke results in increased oxidant damage linked to heart and respiratory diseases. The new findings provide support for efforts to minimize exposure of nonsmokers to environmental tobacco smoke and oxidizing air pollutants and demonstrate the importance of vitamin C for antioxidant protection.

Topics: Ascorbic Acid; Heart Diseases; Humans; Oxidants; Respiratory Tract Diseases; Tobacco Smoke Pollution

Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves, especially in autumn. They are rich in seeds, citrus fruits, olive oil, tea, and red wine. They are low molecular weight compounds composed of a three-ring structure with various substitutions. This basic structure is shared by tocopherols (vitamin E). Flavonoids can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3, or a hydroxyl group in position 3 of the C (middle) ring. These characteristics appear to also be required for best activity, especially antioxidant and antiproliferative, in the systems studied. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities, especially in inhibition of mast cell secretion. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. In spite of the voluminous literature available, however, Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional. Suggestions are made where such possibilities may be worth pursuing.

Topics: Animals; Antioxidants; Antiviral Agents; Ascorbic Acid; Blood Platelets; Coronary Disease; Cytoprotection; Enzyme Inhibitors; Flavonoids; Heart Diseases; Humans; Immune System; Inflammation; Lymphocytes; Mast Cells; Neoplasms; Xenobiotics

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Fruit; Heart Diseases; Humans; Neoplasms; Nutritional Requirements; Vegetables; Vitamin E; Vitamins

The known literature data concerning the mechanisms of molecular action of vitamin E in biological membrane systems are reviewed. The role of vitamin E, possessing a broad range of biological activities, as a universal stabilizer of biological membranes in normal oxygen metabolism and peroxidation, and also in disorders of normal metabolism resulting in pathological alterations, has been discussed. The participation of vitamin E in redox reactions taking place in lipid media, its interaction with singlet oxygen, free fatty acids and enzyme systems are considered. Physiological effects of vitamin E and its ability to prevent numerous pathologies are also considered. Vitamin E was concluded to be a universal participant of antioxidant defence reactions in biological membranes, since it acts at all stages of membrane oxidative damage.

Topics: Aging; Antioxidants; Ascorbic Acid; Fatty Acids, Unsaturated; Free Radicals; Glutathione; Heart Diseases; Humans; Kidney Diseases; Lipid Peroxidation; Liver Diseases; Membranes; Neoplasms; Vitamin E

Circulating free iron is lethal. Humans have two circulating iron binding proteins to soak up free iron to prevent it from generating toxic quantities of free radicals. These proteins are transferrin, a high-affinity, low-capacity protein (2 atoms of iron per molecule of transferrin) for which there are receptors on the surface of every iron-requiring cell; and ferritin, a lower-affinity, high-capacity protein (maximum of 4500 atoms of iron per molecule of ferritin) for which there are receptors only on the surface of iron-storage cells such as RE (reticulo-endothelial) cells. Iron is trapped inside the ferritin protein shell as harmless Fe3. When there is a high serum level of reduced ascorbic acid, it drives through the pores of the ferritin protein shell to the inside surface, where it converts the Fe3 to catalytic Fe2, which then leaks out of the pores of the ferritin protein shell and generates billions of free radicals. In normal individuals, per milliliter of serum, there are approximately 300,000 molecules of transferrin per molecule of ferritin. Ferritin protein is an acute phase reactant that sharply rises in the presence of inflammation of any kind, whereas transferrin is a reverse acute phase reactant that falls in the presence of inflammation of any kind.

Topics: Ascorbic Acid; Ferritins; Free Radicals; Heart Diseases; Humans; Iron; Neoplasms

This paper presents a review of the significant body of literature liking dietary iron overload, not only to heart disease, but also to cancer, diabetes, osteoporosis, arthritis, and possibly other disorders. Following an analysis of our understanding of the mechanistic role iron plays in oxidative damage, an interpretation of the fact that plasma concentrations of several antioxidants are decreased in the presence of disease is offered. Evaluation of (1) age-related dietary trends over time and (2) factors involved in iron absorption leads to the hypothesis that the combination of citric acid and ascorbic acid (a synergistic pair of strong enhancers) is instrumental in causing a deleterious increase in iron load in aging populations. Iron overload may be the most important common etiologic factor in the development of the diseases mentioned; therefore, the synergistic combination of citric and ascorbic acids may play a major role in our worsening disease statistics. Evidence to support this hypothesis and possible experiments to test it are included. This combination needs further study, particularly because the iron overload produced may be correctable.

Topics: Aging; Ascorbic Acid; Citrates; Citric Acid; Diet; Disease; Free Radicals; Heart Diseases; Humans; Intestinal Absorption; Iron; Neoplasms

Iron is a double-edged sword. In moderate quantities and leashed to protein, it is an essential element in all cell metabolism and growth, but it is toxic when unleashed. Because of its ability to switch back and forth between ferrous and ferric oxidation states, iron is both a strong biological oxidant and reductant. The human diet contains a multitude of natural chemicals which are carcinogens and anticarcinogens, many of which act by generating oxygen radicals, which initiate degenerative processes related to cancer, heart disease and aging (the "oxygen radical hypothesis of aging"). Among these many dietary chemicals are many redox agents, including vitamin C and beta carotene. Free radical damage is produced primarily by the hydroxyl radical (.OH). Most of the .OH generated in vivo comes from iron-dependent reduction of H2O2. Supporting too much iron as a free radical-generating culprit in the risk of cancer, NHANES I data indicated that high body iron stores, manifested by increased transferrin saturation, are associated with an increased cancer risk. Other data shows an increased heart attack risk.

Topics: Animals; Anticarcinogenic Agents; Apoferritins; Ascorbic Acid; Carcinogens; Deferoxamine; Diet; Ferritins; Free Radicals; Heart Diseases; Hemin; Humans; Iron; Neoplasms; Oxidation-Reduction; Superoxides

Topics: Adolescent; Adult; Ascorbic Acid; Blood Transfusion; Cardiomyopathies; Deferoxamine; Dose-Response Relationship, Drug; Ferritins; Growth Disorders; Heart Diseases; Hemosiderosis; Humans; Iron; Iron Chelating Agents; Liver; Liver Diseases; Pancreatic Diseases; Parathyroid Diseases; Pituitary Diseases; Thyroid Function Tests

The 'antioxidant hypothesis' proposes that vitamin C, vitamin E, carotenoids, and other antioxidants occurring in fruit and vegetables afford protection against heart disease and cancer by preventing oxidative damage to lipids and to DNA, respectively. To test elements of this hypothesis, we have measured blood levels of dietary antioxidants, and 8-oxodeoxyguanosine (8-oxo-dG) concentrations in lymphocyte DNA, in healthy men and women from five European countries: France, Ireland, The Netherlands, Spain, and the U.K. Volunteers, aged 25 45, all nonsmokers, gave blood samples before and after a 12-wk carotenoid supplementation regime. Vitamin C was measured in plasma and vitamin E and carotenoids were measured in serum by high-performance liquid chromatography (HPLC). 8-oxo-dG was assayed by HPLC (with coulometric detection) in DNA isolated from lymphocytes from the same blood samples. Mean values were calculated for groups of volunteers at each sampling time according to country, sex, and supplementation (between 9 and 24 individual samples contributing to each mean). We found that 8-oxo-dG levels in lymphocyte DNA vary significantly according to sex and country. A low mean 8-oxo-dG concentration is seen in DNA of women from all five countries, and of men from France and Spain. 8-oxo-dG is significantly higher (up to about threefold) in lymphocyte DNA from men in Ireland and the U.K. Oxidative DNA damage is not significantly affected by carotenoid supplementation; nor is there any association with mean baseline levels of antioxidants, which are generally similar in the five countries. The five countries sampled lie on an axis from northern to southern Europe with a steep gradient in terms of premature heart disease. There is a strong association between premature coronary heart disease mortality in men and the mean levels of 8-oxo-dG for the five countries (r = 0.95, P < 0.01). Women have low coronary heart disease mortality rates, which do not correlate with 8-oxo-dG. In terms of cancer deaths, only colorectal cancer in men shows a significant positive correlation (r = 0.91, P < 0.05), and stomach cancer in women is negatively correlated with DNA oxidation (r = -0.92, P = 0.01).

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Antioxidants; Ascorbic Acid; Carotenoids; Chemoprevention; Deoxyguanosine; DNA Damage; Ethnicity; Europe; Female; Heart Diseases; Humans; Lutein; Lycopene; Lymphocytes; Male; Middle Aged; Neoplasms; Oxidation-Reduction; Palm Oil; Plant Oils; Reactive Oxygen Species; Sex Factors; Single-Blind Method; Vitamin E

There is emerging evidence exhibiting the strong association of gut microbiota with cardiovascular metabolic functions. Cardiac diseases may alter the richness, diversity, and composition of the gut microbiome. Vitamin C (Vit C) plays an important role in many metabolic activities in cardiovascular diseases. In this study, we induced cardiac remodeling by the forced swim stress model in rats, which resulted in dysbiosis. Adult male Wistar rats were designated into the following groups: (i) normal control (NC), (ii) forced swim induced stress (FSIS) control, (iii) FSIS + Vit C treatment, and (iv) Vit C control. Stool samples were collected for estimation for 90 days, and at the end of the study, the animals were killed and heart tissue was isolated for histochemical analysis. We observed a sharp fall in the operational taxonomic unit in the FSIS control animals as compared to NC animals. Treatment with Vit C exhibited a decrease in Bacteroidetes while raising the abundance of spirochetes. Plasma levels of creatine kinase myocardial band (CKMB) in the treatment group reduced to 175.7 ± 3.41 U/L, from 317.7 ± 34.48 U/L in the diabetic control group. Also, the C-reactive protein level in the disease control group was 18 ± 0.93 mg/dl, which reduced to the normal level of 7.53 ± 0.20 mg/dl on treatment with Vit C administration. Our results suggest that FSIS induced cardiac complication is also associated with changes in gut microbial abundance. Higher doses of Vit C, which strengthens the immunity, have shown some positive outcomes on cardiac complications. The abundance of gut microbiota is also associated with the immune system, which in turn marks the impact of a disease. More the richness and diversity of the gut microbiome, healthier is the composition that can withstand the external threats of disease and other major challenges in the environment. Hence microbiome abundance plays an important role in the therapies or future prospects of disease. Histopathological studies support the serological and microbiome examination and warrant the cardioprotective influence of Vit C in the stress-induced cardiac dysfunction model.

Topics: Animals; Ascorbic Acid; Dysbiosis; Gastrointestinal Microbiome; Heart Diseases; Male; Rats; Rats, Wistar

Iron deficiency anemia (IDA) in patients with heart disease is correlated with decreased exercise capacity and poor health-related quality of life, and predicts worse cardiovascular outcomes, especially for elderly patients. IDA can worsen cardiac function that can be monitored with Heart Rate Variability (HRV) analysis, providing important information about cardiac health. In a recent study we explored the effect and the tolerability of the administration of Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel Forte®) in "frailty" patients with secondary anemia and low kidney failure, by analysing the HRV frequency domain. The aim of the present study is the further confirmation of the safety of the already evaluated intervention, by analysing non-linear domain of HRV.. In this pilot study we enrolled 52 "frailty" elderly patients, with a recent diagnosis of secondary anemia due to iron deficiency, with Class II New York Heart Association (NYHA) hypertensive heart disease, low kidney failure, and atherosclerosis. The patients were divided in 2 groups: Group A (N=23 patients) received oral administration of Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel Forte®) 2 tabs/day, containing 60 mg of Fe3+, for 24 days; Group B (N=29 patients) received intravenous administration of ferrous gluconate 63 mg/day added to saline solution, while they were hospitalized (15±5 days). We evaluated laboratory values of hemoglobin (Hb) and sideremia levels. Furthermore, we measured ECG signals before and after treatment, using non-linear analysis techniques.. Both intravenous and oral treatments evaluated in this study, were effective and safe about the cardiovascular risk in "frailty" elderly patients, as resulted from non-linear HRV analysis. Efficacy results showed that hemoglobin and sideremia levels after treatments are significantly increased. The HRV non-linear analysis showed that all parameters evaluated, except for the SD1 values in the Group A, were not affected by treatments, confirming the absence of cardiovascular risk of the therapy.. Non-linear HRV evaluation confirmed that oral administration of Ferric Sodium EDTA, in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel forte®) did not impact the cardiovascular risk, without causing adverse events typically reported with other iron supplementation therapies, both oral and intravenous.

Topics: Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Ascorbic Acid; Drug Combinations; Edetic Acid; Female; Ferric Compounds; Folic Acid; Frail Elderly; Frailty; Gluconates; Heart Disease Risk Factors; Heart Diseases; Heart Rate; Humans; Iron Chelating Agents; Male; Pilot Projects; Renal Insufficiency; Risk Assessment; Selenomethionine; Time Factors; Treatment Outcome

Arsenic trioxide (As

Topics: alpha-Tocopherol; Animals; Antioxidants; Apoptosis; Arsenic Trioxide; Arsenicals; Ascorbic Acid; Cardiotoxicity; Cell Line; Cytoprotection; Heart Diseases; Membrane Potential, Mitochondrial; Mitochondria, Heart; Myocytes, Cardiac; NF-E2-Related Factor 2; Oxidative Stress; Oxides; Proto-Oncogene Proteins c-bcl-2; Rats; Signal Transduction

Topics: Acetylcholinesterase; Adenosine Triphosphatases; Animals; Ascorbic Acid; Barium Compounds; Chlorides; Diet; Gene Expression Regulation, Enzymologic; Heart; Heart Diseases; Hydrogen Peroxide; Lipid Peroxidation; Myocardium; Organ Size; Rats; Rats, Wistar; Selenium; Sodium-Potassium-Exchanging ATPase

Topics: Ascorbic Acid; Cardiovascular Diseases; Diet; Fruit; Heart Diseases; Humans; Vegetables

Cardiovascular disease is one of the most significant causes of mortality in humans and animals, and its etiology is usually unknown. The aim of this study was to investigate the cardiac pathology of endosulfan toxicity and the protective effect of vitamin C in rabbits. Twenty-four rabbits were divided into 4 groups: (1) the END group was given a daily sublethal dose of endosulfan in corn oil by oral gavage for 6 weeks; (2) the END + C group received the endosulfan as well as vitamin C over the same 6-week period; (3) the OIL + C group received corn oil daily and vitamin C every other day; and (4) the OIL group received only corn oil daily. We observed microscopic hemorrhages, single-cell necrosis, inflammatory reactions, and fibrotic changes in the myocardium in the END group. Small hemorrhages and single-cell necrosis also were seen in some hearts in the END + C group, but no inflammation was observed. Caspase-3 immunoreactivity was more significant in myocardial cells in the END group compared with the others. A protective effect of vitamin C on lesions was observed in the END + C group. These results showed that endosulfan resulted in toxic changes in the hearts of rabbits, but this toxicity could be decreased with vitamin C treatment.

Topics: Administration, Oral; Animals; Apoptosis; Ascorbic Acid; Cardiotoxins; Caspase 3; Disease Models, Animal; Dose-Response Relationship, Drug; Endosulfan; Fibrosis; Heart Diseases; Insecticides; Male; Myocytes, Cardiac; Necrosis; Rabbits

Cardiovascular progenitor cells (CVPCs) derived from human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), hold great promise for the study of cardiovascular development and cell-based therapy of heart diseases, but their applications are challenged by the difficulties in their efficient generation and stable maintenance. This study aims to develop chemically defined systems for robust generation and stable propagation of hPSC-derived CVPCs by modulating the key early developmental pathways involved in human cardiovascular specification and CVPC self-renewal. Herein we report that a combination of bone morphogenetic protein 4 (BMP4), glycogen synthase kinase 3 (GSK3) inhibitor CHIR99021 and ascorbic acid is sufficient to rapidly convert monolayer-cultured hPSCs, including hESCs and hiPSCs, into homogeneous CVPCs in a chemically defined medium under feeder- and serum-free culture conditions. These CVPCs stably self-renewed under feeder- and serum-free conditions and expanded over 10(7)-fold when the differentiation-inducing signals from BMP, GSK3 and Activin/Nodal pathways were simultaneously eliminated. Furthermore, these CVPCs exhibited expected genome-wide molecular features of CVPCs, retained potentials to generate major cardiovascular lineages including cardiomyocytes, smooth muscle cells and endothelial cells in vitro, and were non-tumorigenic in vivo. Altogether, the established systems reported here permit efficient generation and stable maintenance of hPSC-derived CVPCs, which represent a powerful tool to study early embryonic cardiovascular development and provide a potentially safe source of cells for myocardial regenerative medicine.

Topics: Ascorbic Acid; Bone Morphogenetic Protein 4; Cell Culture Techniques; Cell Differentiation; Cell- and Tissue-Based Therapy; Cells, Cultured; Embryonic Stem Cells; Glycogen Synthase Kinase 3; Heart; Heart Diseases; Humans; Induced Pluripotent Stem Cells; Myocardium; Pyridines; Pyrimidines

To evaluate the effects of alpha-lipoic acid (AL) in a model of doxorubicin (DOX)-induced cardiotoxicity, male Wistar rats were treated with DOX (1 mg/kg/d; 10 d) in combination or not with AL (50 mg/kg/d; 15 d). Plasma oxidative stress was determined by hydroperoxides (ROOH) and the ascorbyl radical/ascorbate ratio. One and two months later, the functional parameters of the hearts were determined in vivo by catheterization and cardiac oxidative stress was assessed by malonedialdehyde (MDA) and O₂*⁻ (dihydroethidium fluorescence) content in tissue. After two months, body weight was higher in the DOX-AL group than in DOX (+16%), but this was due to ascites. Histological liver alterations were observed in both the DOX and DOX-AL groups. Plasma ROOH concentrations decreased after 10 days of AL treatment, but were greater in both the DOX and DOX-AL groups. After two months, a decrease in the cardiac contractility index (-27% and -29%, respectively) and cardiac hypertrophy were observed in DOX and DOX-AL. These dysfunctions were associated with 1) a reduction in plasma ascorbate levels and an increase in the ascorbyl/ascorbate ratio and 2) an increase MDA and O₂*⁻ content in cardiac tissue. In conclusion, a cumulative dose of 10 mg/kg doxorubicin induced functional alterations in the heart associated with plasma and cardiac oxidative stress. The co-administration of the antioxidant compound AL had no beneficial effects in this situation.

Topics: Animals; Antibiotics, Antineoplastic; Antioxidants; Ascitic Fluid; Ascorbic Acid; Body Weight; Cardiotonic Agents; Cardiotoxins; Doxorubicin; Eating; Heart; Heart Diseases; Hematocrit; Hydrogen Peroxide; Liver; Male; Myocardium; Organ Size; Oxidative Stress; Rats; Rats, Wistar; Superoxides; Thiobarbituric Acid Reactive Substances; Thioctic Acid

Fetal hypoxia is a common complication of pregnancy. It has been shown to programme cardiac and endothelial dysfunction in the offspring in adult life. However, the mechanisms via which this occurs remain elusive, precluding the identification of potential therapy. Using an integrative approach at the isolated organ, cellular and molecular levels, we tested the hypothesis that oxidative stress in the fetal heart and vasculature underlies the molecular basis via which prenatal hypoxia programmes cardiovascular dysfunction in later life. In a longitudinal study, the effects of maternal treatment of hypoxic (13% O(2)) pregnancy with an antioxidant on the cardiovascular system of the offspring at the end of gestation and at adulthood were studied. On day 6 of pregnancy, rats (n = 20 per group) were exposed to normoxia or hypoxia ± vitamin C. At gestational day 20, tissues were collected from 1 male fetus per litter per group (n = 10). The remaining 10 litters per group were allowed to deliver. At 4 months, tissues from 1 male adult offspring per litter per group were either perfusion fixed, frozen, or dissected for isolated organ preparations. In the fetus, hypoxic pregnancy promoted aortic thickening with enhanced nitrotyrosine staining and an increase in cardiac HSP70 expression. By adulthood, offspring of hypoxic pregnancy had markedly impaired NO-dependent relaxation in femoral resistance arteries, and increased myocardial contractility with sympathetic dominance. Maternal vitamin C prevented these effects in fetal and adult offspring of hypoxic pregnancy. The data offer insight to mechanism and thereby possible targets for intervention against developmental origins of cardiac and peripheral vascular dysfunction in offspring of risky pregnancy.

Topics: Animals; Arteries; Ascorbic Acid; Female; Heart Diseases; Hypoxia; Longitudinal Studies; Male; Myocardial Contraction; Oxidative Stress; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Vascular Diseases

The Pringle maneuver is a surgical procedure to minimize hemorrhage during hepatectomy, which however, can induce production of reactive oxygen species causing remote organ injury. We sought to study the impact of the Pringle maneuver on cardiac function as well as the protective effects of L-ascorbic acid and α-tocopherol pretreatments.. Rats were divided into four study groups: L-ascorbic acid (60 mg/kg/d) or α-tocopherol (200 mg/kg/d), and surgical interventions (Sham-operated or liver ischemia-reperfusion [I/R]). Liver ischemia was performed by clamping the hepatic artery and portal vein for 30 minutes, followed by reperfusion by releasing the clamps for 2 hours. Cardiac function was evaluated by a high-fidelity pressure-volume catheter positioned in the left ventricle. Myocardial injury was assessed through plasma creatine kinase-MB (CKMB) and troponin I (cTnI). Cardiac lipid peroxidation and systemic hydroxyl radical levels were assessed by cardiac tissue malondialdehyde and plasma methylguanidine, respectively.. Cardiac function was significantly depressed in the I/R group, where plasma CKMB and cTnI were markedly increased (P < .05). L-ascorbic acid and α-tocopherol pretreatments improved cardiac function and significantly reduced cardiac injury (P < .05). L-ascorbic acid pretreatment demonstrated better heart protection than α-tocopherol, in terms of cTnI and CKMB (P < .05), but no significant difference in terms of cardiac functional improvement.. L-ascorbic acid and α-tocopherol pretreatment 3 days prior to the Pringle maneuver attenuated myocardial injury and protected cardiac function by scavenging hydroxyl radical and reducing lipid peroxidation. L-ascorbic acid demonstrated better protection than α-tocopherol.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; Biomarkers; Cardiac Catheterization; Creatine Kinase, MB Form; Disease Models, Animal; Heart Diseases; Hepatectomy; Hydroxyl Radical; Lipid Peroxidation; Liver Diseases; Malondialdehyde; Methylguanidine; Myocardial Contraction; Myocardium; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Time Factors; Troponin I; Ventricular Function, Left; Ventricular Pressure

Present study evaluates cardioprotective role of melatonin (Mel), alpha lipoic acid (ALA), a combination of melatonin and alpha lipoic acid (Mel + ALA) against cadmium (Cd)-induced oxidative damage. Female albino rats were subjected to 15-day exposure to Cd (5.12 mg/kg bw) alone or treated with ML (10 mg/kg bw) + ALA (25 mg/kg bw) simultaneously. Plasma markers of cardiac damage, cardiac free radical generation, lipid peroxidation, endogenous antioxidant status, cadmium load, metallothionein induction, and histopathology were evaluated in various experimental groups. Combination of Mel + ALA significantly prevented leakage of marker enzymes of cardiac damage, changes in cardiac free radical generation, endogenous antioxidants, antioxidant status, structural alterations and augmented the degree of metallothionein (MT) induction. The results demonstrate that ML + ALA co-administration effectively protected against Cd-induced cardiac oxidative damage.

Topics: Animals; Antioxidants; Ascorbic Acid; Biomarkers; Cadmium Chloride; Drug Synergism; Drug Therapy, Combination; Enzymes; Female; Glutathione; Heart Diseases; Hydrogen Peroxide; Hydroxyl Radical; Lipid Peroxidation; Malondialdehyde; Melatonin; Metallothionein; Myocardium; Oxidative Stress; Rats; Thioctic Acid; Vitamin E

The aim of this study was to determine the effects of enrofloxacin (ENR), flunixin meglumine (FM) and dexamethasone (DEX) on antioxidant status and organ damage markers in experimentally-induced endotoxemia. Rats were divided into three groups. To induce endotoxemia, lipopolysaccharide (LPS) was injected into all groups, including the positive control. The two other groups received the following drugs (simultaneously with LPS): ENR + FM + low-dose DEX and ENR + FM + high-dose DEX. After the treatments, blood samples were collected at 0, 1, 2, 4, 6, 8, 12, 24 and 48 h. Oxidative stress parameters were determined by ELISA, while serum organ damage markers were measured by autoanalyser. LSP increased (p < 0.05) malondialdehyde, 13,14-dihydro-15-keto-prostaglandin F(2 alpha) and nitric oxide, while LPS reduced vitamin C. These changes were especially inhibited (p < 0.05) by ENR + FM + high-dose DEX. LPS increased organ damages markers. Cardiac and hepatic damage was not completely inhibited by any treatment, whereas renal damage was inhibited by two treatments. This study suggested that ENR + FM + high-dose DEX is most effective in the LPS-caused oxidative stress and organ damages.

Topics: Animals; Ascorbic Acid; Autoanalysis; Biomarkers; Clonixin; Dexamethasone; Dinoprost; Disease Models, Animal; Drug Therapy, Combination; Enrofloxacin; Enzyme-Linked Immunosorbent Assay; Female; Fluoroquinolones; Heart Diseases; Kidney Diseases; Lipopolysaccharides; Liver Diseases; Male; Malondialdehyde; Multiple Organ Failure; Nitric Oxide; Oxidative Stress; Rats; Rats, Sprague-Dawley; Shock, Septic; Superoxide Dismutase; Time Factors

Topics: Antioxidants; Ascorbic Acid; Heart Diseases; Humans; Treatment Outcome; Vitamin B Complex; Vitamin E

Induction of hyperadrenergic activity was experimentally achieved in urethane-anesthetized rats using epinephrine (adrenaline). Acute administration of epinephrine (100 microg/kg) for 2 hours induced several cardiac disorders and vasomotor dysfunction. Pretreatment with natural wild honey (5 g/kg) for 1 hour prior to the injection with epinephrine (100 mug/kg) protected the anesthetized normal rats from the incidence of epinephrine-induced cardiac disorders and vasomotor dysfunction. Moreover, posttreatment with natural wild honey (5 g/kg) following the injection with epinephrine (100 microg/kg) for 1 hour showed several ameliorative outcomes to the electrocardiographic parameters and vasomotor dysfunction of anesthetized stressed rats. Furthermore, natural wild honey preserved the positive inotropic effect of epinephrine in both cases. Also, the total antioxidant capacity (AOC) of natural wild honey was found to be very pronounced. Levels of both reduced glutathione and ascorbic acid (vitamin C) were considered relatively high in natural wild honey. Activity of superoxide dismutase (SOD) was also high, whereas catalase activity was relatively low, especially when compared to the value of SOD activity. It would appear from the results of the present study that natural wild honey may exert its cardioprotective and therapeutic effects against epinephrine-induced cardiac disorders and vasomotor dysfunction directly, via its very pronounced total AOC and its great wealth of both enzymatic and nonenzymatic antioxidants involved in cardiovascular defense mechanisms, besides its substantial quantities of mineral elements such as magnesium, sodium, and chlorine, and/or indirectly, via the enhancement of the endothelium-derived relaxing factor nitric oxide release through the influence of ascorbic acid (vitamin C).

Topics: Animals; Antioxidants; Ascorbic Acid; Autonomic Nervous System Diseases; Catalase; Electrocardiography; Epinephrine; Glutathione; Heart Diseases; Honey; Male; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Vasomotor System

We prospectively investigated relationships between blood markers of Fe, vitamin B12, folate, vitamin C and vitamin D status and subsequent all-cause mortality in 208 men and 191 women aged 75 years or over living in the community in Aberdeen, Scotland. The participants had been recruited for a cross-sectional study in 1999-2000 when they completed health and lifestyle questionnaires and had blood samples taken for analysis of serum ferritin, serum vitamin B12, erythrocyte folate, plasma vitamin C and serum 25-hydroxycholecalciferol. Mortality was ascertained on national databases up to December 2005, with a median time of follow up of 69.2 (range 1.0-79.9) months. Participants were divided into sex-specific quintiles of baseline levels for each nutrient, and hazard ratios were estimated with Cox proportional hazard models adjusted for age and sex with the significance of linear trends in the associations assessed by logistic regression. There was no significant association between blood markers of Fe, vitamin B12 or folate status at baseline and mortality, but vitamin D status at baseline was inversely related to mortality (P for trend < 0.001). For vitamin C there was no evidence of a linear trend but participants in the lowest quintile of plasma levels had a significantly higher risk of death than those in the highest quintile. Randomized controlled trials of lifestyle changes which improve vitamin status are needed to assess whether these associations could be causal.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Dietary Supplements; Female; Folic Acid; Heart Diseases; Humans; Iron; Life Style; Male; Mortality; Nutritional Status; Prospective Studies; Risk Assessment; Scotland; Self Concept; Sex Distribution; Socioeconomic Factors; Vitamin B 12; Vitamin D

The consumption of diets rich in plant foods are associated with a reduced risk of cardiovascular diseases. This study was aimed to evaluate the role of S-allylcysteine (SAC) in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Subcutaneous injection of ISO (150 mg/kg) to Wistar rats showed a significant decrease in the activities of marker enzymes such as creatine kinase, lactate dehydrogenase, aspartate and alanine transaminases in heart and a significant increase in the levels of thiobarbituric acid reactive substances and lipid hydroperoxides in plasma and heart. ISO-induced rats also showed a significant decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase in heart and the levels of glutathione and ascorbic acid in plasma and heart. Oral administration of SAC (100 and 150 mg/kg) to ISO-treated rats daily for a period of 45 days caused a significant increase in the activities of marker enzymes and improved the antioxidant status by decreasing lipid peroxidative products and increasing the activities of antioxidant enzymes and the levels of nonenzyomic antioxidants. Administration of SAC to normal rats did not show any significant effect. Histopathological findings of the myocardial tissue showed a protective role of SAC in ISO-treated rats. The effect at a dose of 150 mg/kg of SAC was more pronounced than that of the dose 100mg/kg and brought back all the parameters to near normal. The effect exerted by 100 mg/kg of SAC was similar to that of alpha-tocopherol (60 mg/kg). The results of our study show that SAC possesses antioxidant activity in ISO-induced experimental MI.

Topics: Adrenergic beta-Agonists; Animals; Antioxidants; Ascorbic Acid; Cysteine; Glutathione; Heart Diseases; Isoproterenol; Lipid Peroxides; Male; Myocardium; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Tocopherols

Disruption of mitochondria and free radical mediated tissue injury have been reported during cardiotoxicity induced by isoproterenol (ISO), a beta-adrenergic catecholamine. The present study was designed to investigate the effect of the combination of ferulic acid (FA) and ascorbic acid (AA) on the mitochondrial damage in ISO induced cardiotoxicity. Induction of rats with ISO (150 mg/kg b.wt., i.p.) for 2 days resulted in a significant decrease in the activities of respiratory chain enzymes (NADH dehydrogenase and cytochrome c-oxidase), tricarboxylic acid cycle enzymes (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, alpha-ketoglutarate dehydrogenase), mitochondrial antioxidants (GPx, GST, SOD, CAT, GSH), cytochromes (b, c, c1, aa3) and in the level of mitochondrial phospholipids. A marked elevation in mitochondrial lipid peroxidation, mitochondrial levels of cholesterol, triglycerides and free fatty acids were also observed in ISO intoxicated rats. Pre-co-treatment with the combination of FA (20 mg/kg b.wt.) and AA (80 mg/kg b.wt.) orally for 6 days significantly enhanced the attenuation of these functional abnormalities and restored normal mitochondrial function when compared to individual drug treated groups. Mitigation of ISO induced biochemical and morphological changes in mitochondria were more pronounced with a combination of FA and AA rather than the individual drug treated groups. Transmission electron microscopic observations also correlated with these biochemical parameters. Hence, these findings demonstrate the synergistic ameliorative potential of FA and AA on mitochondrial function during beta-adrenergic catecholamine induced cardiotoxicity and associated oxidative stress in rats.

Topics: Adrenergic beta-Agonists; Animals; Ascorbic Acid; Coumaric Acids; Cytochromes; Drug Synergism; Glutathione; Heart Diseases; Isoproterenol; Lipid Peroxides; Male; Microscopy, Electron, Transmission; Mitochondria, Heart; Rats; Rats, Wistar

Patients with iron overload frequently suffer from hemochromatosis of major organs, such as the heart and liver. Heart affection is the most common cause of death in patients with iron overload. Although the beneficial effects of deferoxamine (DFO) on iron-associated mortality are well documented, the role of deferiprone in the management of transfusional iron overload is controversial. The aim of this study was to compare the protective effect of iron chelators (DFO and deferiprone) individually and in combination with the anti-oxidant (vitamin C) in the prevention of myocardial damage. Sixty albino rats were divided into six groups: two control groups (noniron-loaded and iron-loaded) and four iron-loaded groups classified as follows: DFO group, DFO combined with vitamin C group, deferiprone group and deferiprone combined with vitamin C group. Heart tissue and blood samples were taken for histopathological examination of the heart, determination of total iron-binding capacity, 8-OH-deoxyguanosine (8-OH-dG), myocardial lipid peroxidation and glutathione (GSH) content. Less histopathological cardiac changes and a significant decrease in all biochemical parameters, except myocardial GSH, were observed in the deferiprone group. The addition of vitamin C improves the biochemical and histopathological changes in comparison to those rats administered DFO or deferiprone individually.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Ascorbic Acid; Deferiprone; Deferoxamine; Deoxyguanosine; Glutathione; Heart; Heart Diseases; Iron; Iron Chelating Agents; Iron Overload; Male; Myocardium; Pyridones; Rats; Thiobarbituric Acid Reactive Substances

This study was designed to evaluate the cardioprotective potential of naringin on lipid peroxides, enzymatic and nonenzymatic antioxidants and histopathological findings in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Subcutaneous injection of ISO (85 mg/kg) to male Wistar rats showed a significant increase in the levels of thiobarbituric acid reactive substances and lipid hydroperoxides in plasma and the heart and a significant decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in the heart and the levels of reduced glutathione, vitamin C and vitamin E in plasma and heart and ceruloplasmin in plasma. Oral administration of naringin (10, 20 and 40 mg/kg, respectively) to ISO-induced rats daily for a period of 56 days showed a significant decrease in the levels of lipid peroxidative products and improved the antioxidant status by increasing the activities of antioxidant enzymes and nonenzymatic antioxidants. Histopathological findings of the myocardial tissue showed the protective role of naringin in ISO-induced rats. The effect at a dose of 40 mg/kg of naringin was more pronounced than that of the other two doses, 10 and 20mg/kg. The results of our study show that naringin possess anti-lipoperoxidative and antioxidant activity in experimentally induced cardiac toxicity.

Topics: Adrenergic beta-Agonists; Animals; Antioxidants; Ascorbic Acid; Ceruloplasmin; Enzymes; Flavanones; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Heart Diseases; Hydrogen Peroxide; Isoproterenol; Lipid Metabolism; Lipid Peroxides; Lipoproteins; Male; Muscle Fibers, Skeletal; Myocardial Infarction; Myocardium; Rats; Rats, Wistar; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

We have examined the effect of subchronic methidathion (MD) administration on heart damage, and have evaluated possible ameliorating effects of a combination of vitamins E and C against MD toxicity. The experimental groups were: control group, rats treated with 5 mg/kg MD and rats treated with 5 mg/kg body weight MD plus vitamin E and vitamin C (MD+Vit). The groups were given MD by gavage 5 days a week for four weeks at a dose level of 5 mg/kg/day (MD and MD+Vit) by using corn oil as the vehicle. Vitamin E and vitamin C were injected at doses of 50 mg/kg i.m. and 20 mg/kg i.p., respectively, after the treatment with MD in the MD+ Vit group. The levels of malondialdehyde (MDA) were determined in the heart tissue, and the levels of cardiac troponin I (TnI) in serum. An autoanalyser was used to determine the serum activities of cholinesterase (ChE). Histopathological examination was carried out in the heart tissue. MDA significantly increased in the MD group as compared to controls (P <0.01). When MD was given concurrently with vitamins E and C, the increase in MDA was significantly less (P <0.01). ChE activity significantly decreased in the MD group as compared to controls (P <0.01). When MD was given concurrently with vitamins E and C, the decrease in ChE activity was significantly higher (P <0.05). The serum TnI levels significantly increased in the MD group as compared to controls (P <0.01). When MD was given concurrently with vitamins E and C, the increase in the serum TnI was significantly less (P <0.01). MD caused the diffuse loss of striation and myocytolysis of the cardiomyocytes, whereas the combination of vitamins E and C caused a significant decrease in these effects of MD. In conclusion, subchronic MD administration caused heart damage and, in addition, treatment with a combination of vitamins E and C after the administration of MD reduced heart damage caused by MD.

Topics: Animals; Antioxidants; Ascorbic Acid; Biomarkers; Cholinesterases; Drug Therapy, Combination; Heart Diseases; Insecticides; Lipid Peroxidation; Male; Malondialdehyde; Myocardium; Organothiophosphorus Compounds; Rats; Rats, Wistar; Troponin I; Vitamin E

Topics: Antioxidants; Ascorbic Acid; Follow-Up Studies; Fruit; Heart Diseases; Humans; Vegetables

High body iron stores may increase the risk of several chronic diseases. Whether dietary factors contribute to the risk of high iron stores is unknown.. We assessed the relation between dietary factors and the risk of high iron stores in the elderly Framingham Heart Study cohort.. We examined the relation between the usual intake of dietary factors (food-frequency questionnaire) and the risk of high iron stores (serum ferritin >300 and 200 micro g/L in men and women, respectively) in 614 subjects aged 68-93 y.. The risk of high iron stores was significantly higher 1) in subjects who took > or =30 mg supplemental Fe/d than in nonusers [odds ratio (OR): 4.32; 95% CI: 1.63, 11.47], 2) in subjects who consumed >21 servings of fruit/wk than in those who consumed < or =14 servings/wk (OR: 2.88; 95% CI: 1.26, 6.61), and 3) in subjects who consumed >4 but <7 or > or=7 servings of red meat/wk than in those who consumed < or =4 servings/wk (ORs: 2.94 and 3.61, respectively; 95% CIs: 1.33, 6.47 and 1.57, 8.27, respectively). Whole-grain intake (>7 servings/wk) was inversely associated (OR: 0.23; 95% CI: 0.07, 0.75).. Among elders, intakes of highly bioavailable forms of iron (supplemental iron and red meat) and of fruit, a dietary source of an enhancer of nonheme-iron absorption (vitamin C), promote high iron stores, whereas foods containing phytate (whole grains) decrease these stores. Individual dietary patterns may be important modulators of high iron stores.

Topics: Aged; Aged, 80 and over; Aging; Alcohol Drinking; Animals; Ascorbic Acid; Biological Availability; Body Mass Index; Cohort Studies; Diet; Dietary Supplements; Edible Grain; Female; Ferritins; Fruit; Heart Diseases; Humans; Iron; Iron, Dietary; Longitudinal Studies; Male; Massachusetts; Meat; Reference Values; Risk Factors

It is well known that eating fruits and vegetables lowers the risk of chronic diseases such as heart disease and cancer. The question of what is/are the active ingredient(s) is still unresolved. The initial hypothesis was that the antioxidant vitamins were responsible. However, recently the polyphenols have been investigated since they have been found to have beneficial properties such as being strong antioxidants. We measured the polyphenol content of citrus juices by an oxidation-reduction colorimetric method (Folin) using catechin as the standard. The order was tangerine juice > grapefruit juice > orange juice. The antioxidant contribution of ascorbic acid was measured by the difference in Folin reactive content following removal by ascorbate oxidase. Ascorbate contributed 56 to 77% of the antioxidant content of orange juice, 46% of the single tangerine juice measured, and 66 to 77% of grapefruit juices. Polyphenol quality in the juices was analyzed by using the inhibition of lower density lipoprotein oxidation promoted by cupric ion, an in vitro model of heart disease. Quality decreased in the following order: orange juice > grapefruit juice > tangerinejuice. In orange juice polyphenols accounted for 84-85% of antioxidant quality. The pure polyphenol hesperidin, which is common in juices, ascorbic acid, and the citrus juices, were not able to bind with LDL+VLDL and protect it from oxidation. In a hamster model of atherosclerosis, the juices were able to significantly inhibit atherosclerosis and lowered cholesterol and triglycerides. Ascorbic acid alone in the dose provided by the juices was found to have the same effect on atherosclerosis. However, the polyphenols in the citrus

Topics: Adult; Animals; Antioxidants; Arteriosclerosis; Ascorbic Acid; Beverages; Citrus; Cricetinae; Diet, Atherogenic; Disease Models, Animal; Drug Evaluation; Drug Evaluation, Preclinical; Female; Flavonoids; Heart Diseases; Hesperidin; Humans; Hypercholesterolemia; Hypertriglyceridemia; Lipids; Male; Mesocricetus; Middle Aged; Oxidation-Reduction; Phenols; Plant Extracts; Polymers; Species Specificity

Topics: Antioxidants; Ascorbic Acid; Blood Platelets; Drug Tolerance; Heart Diseases; Humans; NADPH Oxidases; Nitrates; Nitric Oxide; Nitroglycerin; Platelet Aggregation Inhibitors; Superoxides; Vasodilator Agents

The National University of Singapore Heart Study measured cardiovascular risk factors, including selected plasma vitamins, on a random sample of the general population aged 30 to 69 years. Plasma vitamins A and E were normal and similar by ethnic group. Mean plasma vitamin A levels were: Chinese (males 0.68 and females 0.52 mg/L), Malays (males 0.67 and females 0.54 mg/L), and Indians (males 0.66 and females 0.51 mg/L). Mean plasma vitamin E levels were: Chinese (males 12.6 and females 12.6 mg/L), Malays (males 13.6 and females 13.3 mg/L), and Indians (males 12.9 and females 12.8 mg/L). No person had plasma vitamin A deficiency (< 0.01 mg/L) and only 0.1% had vitamin E deficiency (< 5.0 mg/L). In contrast, plasma vitamin C was on the low side and higher in Chinese than Malays and Indians. Mean plasma vitamin C levels were: Chinese (males 6.3 and females 8.4 mg/L), Malays (males 5.1 and females 6.4 mg/L), and Indians (males 5.7 and females 6.9 mg/L). Likewise, the proportions with plasma vitamin C deficiency (< 2.0 mg/L) were lower in Chinese (males 14.4 and females 0.7%), than Malays (males 19.7 and females 7.2%), and Indians (males 17.8 and females 11.0%). Relatively low levels of plasma vitamin C may contribute to the high rates of coronary heart disease and cancer in Singapore. In particular, lower plasma vitamin C in Malays and Indians than Chinese may contribute to their higher rates of coronary heart disease. However, plasma vitamin C does not seem to be involved in the higher rates of cancer in Chinese than Malays and Indians. The findings suggest a relatively low intake of fresh fruits and a higher intake is recommended. Also, food sources of vitamin C may be destroyed by the high cooking temperatures of local cuisines, especially the Malay and Indian ones.

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; China; Cooking; Coronary Disease; Ethnicity; Feeding Behavior; Female; Fruit; Heart Diseases; Humans; India; Malaysia; Male; Middle Aged; Neoplasms; Risk Factors; Singapore; Smoking; Vitamin A; Vitamin E; Vitamin E Deficiency

Topics: Animals; Apolipoprotein A-I; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol, HDL; Female; Heart Diseases; Humans; Male; Rats; Sex Characteristics

Topics: Ascorbic Acid; beta Carotene; Carotenoids; Heart Diseases; Humans; Male; Neoplasms

Topics: Ascorbic Acid; Cohort Studies; Diet; Eating; Heart Diseases; Humans; Neoplasms; Odds Ratio; United States

We examined the relation between vitamin C intake and mortality in the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study cohort. This cohort is based on a representative sample of 11,348 noninstitutionalized U.S. adults age 25-74 years who were nutritionally examined during 1971-1974 and followed up for mortality (1,809 deaths) through 1984, a median of 10 years. An index of vitamin C intake has been formed from detailed dietary measurements and use of vitamin supplements. The relation of the standardized mortality ratio (SMR) for all causes of death to increasing vitamin C intake is strongly inverse for males and weakly inverse for females. Among those with the highest vitamin C intake, males have an SMR (95% confidence interval) of 0.65 (0.52-0.80) for all causes, 0.78 (0.50-1.17) for all cancers, and 0.58 (0.41-0.78) for all cardiovascular diseases; females have an SMR of 0.90 (0.74-1.09) for all causes, 0.86 (0.55-1.27) for all cancers, and 0.75 (0.55-0.99) for all cardiovascular diseases. Comparisons are made relative to all U.S. whites, for whom the SMR is defined to be 1.00. There is no clear relation for individual cancer sites, except possibly an inverse relation for esophagus and stomach cancer among males. The relation with all causes of death among males remains after adjustment for age, sex, and 10 potentially confounding variables (including cigarette smoking, education, race, and disease history).

Topics: Adult; Aged; Ascorbic Acid; Cohort Studies; Diet; Eating; Female; Follow-Up Studies; Heart Diseases; Humans; Male; Middle Aged; Neoplasms; Nutrition Surveys; Population Surveillance; Prospective Studies; Sex Factors; Survival Rate; United States

There has been no report on the determination of uric acid (UA) in human brain and heart tissues. UA and ascorbic acid (AA) in human cerebral cortex and heart tissues excised after cardiac death have been studied by reversed-phase high-performance liquid chromatography (HPLC) with electrochemical detection (ECD). It has been found that the levels of AA and UA in the human cerebral cortex tissues tend to decrease and increase, respectively, after cardiac death as a function of time between death and forensic operation. In addition, it has been found that there is no special relationship between UA levels in human heart tissues and time after cardiac death, also that the UA levels in the heart are high as compared with those in human cerebral cortex tissues. We have emphasized that the HPLC-ECD method is useful in determining UA and AA in mammalian tissues by one-time chromatography to gain a better understanding of the relationship between disease and serum urate level.

Topics: Ascorbic Acid; Cerebral Cortex; Chromatography, High Pressure Liquid; Heart Diseases; Humans; Male; Middle Aged; Postmortem Changes; Uric Acid

The application of noninvasive techniques to the evaluation of cardiac function in iron overload has identified a high incidence of abnormalities in asymptomatic patients prior to the onset of overt cardiac deterioration. Of the tests we have used, radionuclide cineangiography appears to be the most sensitive because it can be conveniently applied during the physiological stress of exercise. Other tests of cardiac function that include stress are also likely to be more sensitive than resting measurements of cardiac function. Systematic application of these techniques to the study of patients on iron chelation therapy should results in an early determination of the efficacy of such treatment.

Topics: Adolescent; Adult; Ascorbic Acid; Child; Child, Preschool; Deferoxamine; Heart; Heart Diseases; Heart Failure; Heart Function Tests; Humans; Iron; Thalassemia; Transfusion Reaction

Homo sapiens' gene pool contains a defective gene for the synthesis of the active enzyme protein, L-gulonolactone oxidase(GLO). The absence of GLO in the human liver blocks the normal mammalian conversion of blood sugar into ascorbate, leading to the potentially-fatal "inborn error of carbohydrate metabolism", the genetic disease, Hypoascorbemia (in the older nomenclature- scurvy). To survive, humans need exogenous sources of daily ascorbate. Most mammals have the intact gene for GLO synthesis and produce generous daily amounts of the liver metabolite, ascorbate; for instance, an unstressed 70 Kg goat is capable of producing over 13 grams of ascorbate daily and much more under stress. The recommended dietary allowance of 45 milligrams of ascorbate a day for human adults, now proposed and used by nutritionists, is grossly inadequate to restore Homo sapiens to a normal mammalian ascorbate physiology. To correct fully this human genetic defect and banish epidemic chronic subclinical scurvy requires daily intakes of ascorbate equivalent to, at least, the amounts synthesized by the other mammals. Humans kept on a long term regime of full correction of this birth defect show great salutary benefits in health maintenance, disease therapy and slowing of the aging process. This can be regarded as the creation of a new and more robust, longer-living, tough human sub-species, Homo sapiens ascorbicus, by the biochemical reversal of a primate mutation occurring some 60 million years ago. Some of the practical benefits and pathways of future clinical research are discussed.

Topics: Aging; Alcohol Oxidoreductases; Ascorbic Acid; Ascorbic Acid Deficiency; Genes; Heart Diseases; Humans; Neoplasms; Substance-Related Disorders; Sudden Infant Death; Virus Diseases

Topics: Adolescent; Ascorbic Acid; Cardiac Catheterization; Child; Child, Preschool; Female; Heart Diseases; Heart Septal Defects; Humans; Indicator Dilution Techniques; Male; Methods

The usefulness of the ascorbate dilution method in demonstrating intracardiac shunts and valvular incompetence is known. The ascorbate technique can also be applied to the determination of the transit time of regional vascular beds such as the coronary and the renal systems. Furthermore, the determination of central circulation times may be helpful in the diagnosis of caval obstruction. The method is safe, simple, inexpensive, and reliable.

Topics: Adolescent; Adult; Ascorbic Acid; Blood Circulation; Coronary Circulation; Evaluation Studies as Topic; Heart Diseases; Humans; Indicator Dilution Techniques; Time Factors

Topics: Ascorbic Acid; Ductus Arteriosus, Patent; Electrocardiography; Heart Aneurysm; Heart Diseases; Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular; Humans; Indicator Dilution Techniques; Pulmonary Valve Insufficiency

Topics: Adolescent; Adult; Ascorbic Acid; Cardiac Catheterization; Diagnosis, Differential; Dye Dilution Technique; Electrocardiography; Female; Fluorocarbon Polymers; Heart Defects, Congenital; Heart Diseases; Humans; Hydrogen; Male; Methods; Phonocardiography; Platinum

Topics: Alcoholism; Ascorbic Acid; Beer; Beriberi; Electrocardiography; Gastritis; Heart Diseases; Humans; Male; Middle Aged; Radiography, Thoracic; Thiamine

Topics: Ascorbic Acid; Blood Protein Electrophoresis; Child; Cyanosis; Genetics, Medical; Heart Diseases; Hemoglobins; Humans; Infant; Infant, Newborn; Methemoglobin; Methemoglobinemia; Methylene Blue; Oxidoreductases; Pathology; Spectrophotometry

Topics: Ascorbic Acid; Diagnosis, Differential; Dogs; Electrocardiography; Heart Defects, Congenital; Heart Diseases; Heart Failure; Humans; Indicator Dilution Techniques; Mitral Valve Insufficiency; Mitral Valve Stenosis; Oximetry; Research

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Ascorbic Acid; Cardiology; Drug Therapy; Heart Diseases; Humans; Pyridoxine

Topics: Animals; Arteriosclerosis; Ascorbic Acid; Cholestanes; Cholesterol; Cortisone; Heart Diseases; Rats; Sclerosis; Vitamin D; Vitamins

Topics: Aged; Ascorbic Acid; Digitalis; Digitalis Glycosides; Heart Diseases; Plant Extracts; Vitamins

Topics: Adrenal Cortex Hormones; Ascorbic Acid; Cardiovascular System; Desoxycorticosterone Acetate; Heart Diseases; Vitamins